Increased mTOR Signaling and Impaired Autophagic Flux Are Hallmarks of SARS-CoV-2 Infection
Érika Pereira Zambalde, Thomaz Lüscher Dias, Grazielle Celeste Maktura, Mariene R. Amorim, Bianca de Freitas Brenha, Luana Nunes Santos, Lucas I Buscaratti, João Gabriel de Angeli Elston, Mariana Camargo Silva Mancini, Isadora Carolina Betim Pavan, Daniel A. Toledo-Teixeira, Karina Bispo-dos-Santos, Pierina Lorencini Parise, Ana Paula Morelli, Luiz Guilherme Salvino da Silva, Ícaro Maia Santos de Castro, Tatiana D. Saccon, Marcelo A. Mori, Fabiana Granja, Helder I. Nakaya, José Luiz Proença‐Módena, Henrique Marques‐Souza, Fernando Moreira Simabuco
Abstract
The COVID-19 (Coronavirus Disease 2019), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affects mainly individuals with pre-existing comorbidities. Here our aim was to correlate the mTOR (mammalian/mechanistic Target of Rapamycin) and autophagy pathways with the disease severity. Through western blotting and RNA analysis, we found increased mTOR signaling and suppression of genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2 as well as in transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients. Immunofluorescence co-localization assays also indicated that SARS-CoV-2 colocalizes within autophagosomes but not with a lysosomal marker. Our findings indicate that SARS-CoV-2 can benefit from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling.